Skip to main content
SpringerLink
Log in

The Immunology of DNA Vaccines

  • Protocol
DNA Vaccines

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 29))

  • 957 Accesses

Abstract

The surprising observation that direct inoculation of an expression plasmid encoding a foreign protein into the skin of mice resulted in the induction of antibody responses, demonstrated that injection of “naked” DNA could result in antigen expression in an immunogenic form (1). This observation and the subsequent demonstration that intramuscular injections of plasmid DNA encoding influenza nucleoprotein could protect mice against a challenge with live influenza virus have opened up new avenues for vaccine development (2–3). Immunization with plasmid DNA has been shown to activate both humoral and cellular immune responses, including the generation of antigen-specific CD8+ cytotoxic T cells as well as CD4+ T helper cells (4). An increasing number of studies using experimental animal models have demonstrated that plasmid DNA immunization can promote effective immune responses against numerous viruses, including influenza, rabies, HIV, HBV, HCV, and HSV; several bacteria, including: Mycobacterium tuberculosis, Mycoplasma pulmonis, and Borrelia burgdorferi; as well as parasites, such as malaria and leishmania (4). Phase I clinical vaccine trials are currently being performed for HIV, HBV, and influenza virus. With the molecular identification of tumor antigens (5), there has also been increasing interest in the development of DNA-based immunization for cancer. Preclinical studies demonstrate that DNA-based immunizations targeting model tumor antigens such as chicken ovalbumin (6), β-galactosidase (7), or CEA (8) induce protective immune responses leading to rejection of a subsequent, normally lethal challenge with antigen-expressing tumor cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tang, D. C., DeVit, M. J., and Johnston, S. A. (1992) Genetic immunization: a simple method for eliciting an immune response. Nature (Lond.) 356, 152–154.

    Article  CAS  Google Scholar 

  2. Ulmer, J. B., Donnelly, J. J., Parker, S. E., Rhodes, G. H., Felgner, P. L., Dwarki, V. J., et al. (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259, 1745–1749.

    Article  CAS  PubMed  Google Scholar 

  3. Fynan, E. F., Webster, R. G., Fuller, D. H., Haynes, J. R., Santoro, J. C., and Robinson, H. L. (1993) DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl. Acad. Sci. USA 90, 11,478–11,482.

    Article  CAS  PubMed  Google Scholar 

  4. Donnelly, J. J., Ulmer, J. B., Shiver, J. W., and Liu, M. A. (1997) DNA vaccines. Ann Rev. Immunol. 15, 617–648.

    Article  CAS  Google Scholar 

  5. Boon, T. and Van der Bruggen, P. (1996) Human tumor antigens recognized by T lymphocytes. J. Exp. Med. 183, 725–729.

    Article  CAS  PubMed  Google Scholar 

  6. Condon, C., Watkins, S. C., Celluzzi, C. M., Thompson, K., and Falo, L. D. (1996) DNA-based immunization by in vivo transfectiion of dendritic cells. Nat. Med. 2, 1122–1128.

    Article  CAS  PubMed  Google Scholar 

  7. Irvine, K. R., Rao, R. B., Rosenberg, S. A., and Restifo, N. P. (1996) Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. J. Immunol. 156, 238–245.

    CAS  PubMed  Google Scholar 

  8. Conry, R. M., Widera, G., LoBuglio, A. F., Fuller, J. T., Moore, S. T., Barlow, D. L., Turner, J., Yang, N.-S., and Curiel, D. T. (1996) Selected strategies to augment polynucleotide immunization. Gene Ther. 3, 67–74.

    CAS  PubMed  Google Scholar 

  9. Pardoll, D. M. and Beckerleg, A. M. (1995) Exposing the immunology of naked DNA. Immunity 3, 165–169.

    Article  CAS  PubMed  Google Scholar 

  10. Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., and Felgner, P. L. (1990) Direct gene transfer into mouse muscle in vivo. Science 247, 1465–1468.

    Article  CAS  PubMed  Google Scholar 

  11. Wolff, J. A., Ludtke, J. J., Acsadi, G., Williams, P., and Jani, A. (1992) Logn-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet. 1, 363–369.

    Article  CAS  PubMed  Google Scholar 

  12. Davis, H. L., Whalen, R. G., and Demeneix, B. A. (1993) Direct gene transfer into skeletal muscle in vivo: Factors affecting efficiency of transfer and stability of expression. Hum. Gene Ther. 4, 151–159.

    Article  PubMed  Google Scholar 

  13. Cheng, L., Ziegelhoffer, P. R., and Yang, N.-S. (1993) In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment. Proc. Natl. Acad. Sci. USA 90, 4455–4459.

    Article  CAS  PubMed  Google Scholar 

  14. Eisenbraun, M. D., Fuller, D. H., and Haynes, J. R. (1993) Examination of parameters affecting the elicitation of humoral immune responses by particle bombardment-mediated genetic immunzation. DNA Cell Biol. 12, 791–797.

    Article  CAS  PubMed  Google Scholar 

  15. Pertmer, T. M., Eisenbraun, M. D., McCabe, D., Prayaga, S. K., Fuller, D. H., and Haynes, J. R. (1995) Gene gun-based nucleic acid immunzation: elicitation of humoral and cytotoxic T-lymphocyte responses following epidermal delivery of nanogram quantites of DNA. Vaccine 13, 1427–1430.

    Article  CAS  PubMed  Google Scholar 

  16. Feltquate, D. M., Heaney, S., Webster, R. G., and Robinson, H. L. (1997) Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 158, 2278–2284.

    CAS  PubMed  Google Scholar 

  17. Raz, E., Carson, D. A., Parker, S. E., Parr, T. B., Abai, A. M., Aichinger, G., et al. (1994) Intradermal gene immunization: the possible role fo DNA uptake in the induction of cellular immunity to viruses. Proc. Natl. Acad. Sci. USA 91, 9519–9523.

    Article  CAS  PubMed  Google Scholar 

  18. Torres, C. A. T., Iwasaki, A., Barber, B. H., and Robbinson, H. L. (1997) Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations. J. Immunol. 158, 4529–4532.

    CAS  PubMed  Google Scholar 

  19. Bos, J. D. and Kapsenberg, M. L. (1993) The skin immune system: progress in cutaneous biology. Immunol. Today 14, 75–78.

    Article  CAS  PubMed  Google Scholar 

  20. Raz, E., Tighe, H., Sato, Y., Corr, M., Dudler, J. A., Roman, M., et al. (1996) Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc. Natl. Acad. Sci. USA 91, 9519–9523.

    Article  Google Scholar 

  21. Pertmer, T. M., Roberts, T. R., and Haynes, J. R. (1996) Influenza virus nucleoprotein-specific immunoglobulin G subclass and cytokine responses elicited by DNA vaccination are dependent on the route of vector DNA delivery. J. Virol. 76, 6119–6125.

    Google Scholar 

  22. Cresswell, P. (1993) Antigen processing. Annu. Rev. Immunol. 11, 259–293.

    Google Scholar 

  23. York, I. A. and Rock, K. L. (1996) Antigen processing and presentation by the class I major histocompatibility complex. Annu. Rev. Immunol. 14, 369–396.

    Article  CAS  PubMed  Google Scholar 

  24. Watts, C. (1997) Capture and processing of exogenous antigens for presentation on MHC molecules. Annu. Rev. Immunol. 15, 821.

    Article  CAS  PubMed  Google Scholar 

  25. Rammensee, H.-G. (1995) Chemistry of peptides associated with MHC class I and II molecules. Curr. Opin. Immunol. 7, 85–96.

    Article  CAS  PubMed  Google Scholar 

  26. Boise, L., Minn, A., Noel, P., June, C., Accavitti, M., Lindsten, T., and Thompson, C. (1995) CD28 costimulation can promote T cell survivial by enhancing the expression of Bcl-xL. Immunity 3, 87.

    Article  CAS  PubMed  Google Scholar 

  27. Steinman, R. M. (1991) The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271–296.

    Article  CAS  PubMed  Google Scholar 

  28. Cella, M., Sallusto, F., and Lanzavecchia, A. (1997) Origin, maturation and antigen presenting function of dendritic cells. Curr. Opin. Immunol. 9, 10–16.

    Article  CAS  PubMed  Google Scholar 

  29. Doe, B., Selby, M., Barnett, S., Baenziger, J., and Walker, C. M. (1996) Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells. Proc. Natl. Acad. Sci. USA 93, 8578–8583.

    Article  CAS  PubMed  Google Scholar 

  30. Corr, M., Lee, D. J., Carson, D. A., and Tighe, H. (1996) Gene vaccination with naked plasmid DNA: mechanism of CTL priming. J. Exp. Med. 184, 1555–1560.

    Article  CAS  PubMed  Google Scholar 

  31. Fu, T.-M., Ulmer, J. B., Caulfield, M. J., Deck, R. R., Friedman, A., Wang, S., et al. (1997) Priming of cytotoxic T lymphocytes by DNA vaccines: Requirements for professional antigen presenting cells and evidence for antigen transfer from myocytes. Mol. Med. 3, 362–371.

    CAS  PubMed  Google Scholar 

  32. Iwasaki, A., Torres, C. A. T., Ohashi, P. S., Robbinson, H. L., and Barber, B. H. (1997) The dominant role of bone marrow-derived cells in CTL induction following plasmid DNA immunization at different sites. J. Immunol. 159, 11–14.

    CAS  PubMed  Google Scholar 

  33. Ulmer, J. B., Deck, R. R., Dewitt, C. M., Donnelly, J. J., and Liu, M. A. (1996) Generation of MHC class I-restricted cytotoxic T lymphocytes by expression of a viral protein in muscle cells: antigen presentation by non-muscle cells. Immunology 89, 59–67.

    Article  CAS  PubMed  Google Scholar 

  34. Condon, C., Watkins, S. C., Celluzzi, C. M., Thompson, K., and Falo, L. D. (1996) DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2, 1122–1128.

    Article  CAS  PubMed  Google Scholar 

  35. Song, E. C., Lee, V., Surh, C. D., Lynn, A., Brumm, D., Jolly, D. J., et al. (1997) Antigen presentation in retroviral vector-mediated gene transfer in vivo. Proc. Natl. Acad. Sci. USA 94, 1943–1948.

    Article  CAS  PubMed  Google Scholar 

  36. Casares, S., Inaba, K., Brumeanu, T.-D., Steinman, R. M., and Bona, C. A. (1997) Antigen presentation by dendritic cells after immuniation with DNA encoding a major histocompatibility complex class II-restricted viral epitope. J. Exp. Med. 186, 1481–1486.

    Article  CAS  PubMed  Google Scholar 

  37. McKinney, E. C. and Streilein, J. W. (1989) On the extraordinary capacity of allogeneic epidermal Langerhans cells to prime cytotoxic T cells in vivo. J. Immunol. 143, 1560–1564.

    CAS  PubMed  Google Scholar 

  38. Timares-Lebow, L., Takashima, A., and Johnston, S. A. (1997) Enhanced immune responses by inoculation of a transfected dendritic cell line (XS106). J. Invest. Derm. 109, 266.

    Google Scholar 

  39. Davis, H. L., Millan, C. L., and Watkins, S. C. (1997) Immune-mediated destruction of transfected muscle fibers after direct gene transfer with antigen-expressing plasmid DNA. Gene Ther. 4, 181–188.

    Article  CAS  PubMed  Google Scholar 

  40. Xiang, Z. and Ertl, H. C. J. (1995) Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2, 129–135.

    Article  CAS  PubMed  Google Scholar 

  41. Conry, R. M., Widera, G., LoBuglio, A. F., Fuller, J. T., Moore, S. T., Barlow, D. L., et al. (1996) Selected strategies to augment polynucleotide immunization. Gene Ther. 3, 67–74.

    CAS  PubMed  Google Scholar 

  42. Kim, J. J., Ayyavoo, V., Bagarazzi, M. L., Chattergoon, M. A., Dang, K., Wang, B., et al. (1997) In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen. J. Immunol. 158, 816–826.

    CAS  PubMed  Google Scholar 

  43. Tsuji, T., Hamajima, K., Fukushima, J., Xin, K.-Q., Ishii, N., Aoki, I., et al. (1997) Enhancement of cell-mediated immunity against HIV-1 induced by coinoculation of plasmid-encoded HIV-1 antigen with plasmid espressing IL-12. J. Immunol. 158, 4008–4013.

    CAS  PubMed  Google Scholar 

  44. Chow, Y. H., Huang, W. L., Chi, W. K., Chu, Y. D., and Tao, M. H. (1997) Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2. J. Virol. 71, 169–178.

    CAS  PubMed  Google Scholar 

  45. Iwasaki, A., Stiernholm, B. J. N., Chan, A. K., Berinstein, N. L., and Barber, B. H. (1997) Enhanced CTL responses mediated by plasmid DNA immunogens encoding costimulatory molecules and cytokines. J. Immunol. 158, 4591–4601.

    CAS  PubMed  Google Scholar 

  46. Lenschow, D. J., Walunas, T. L., and Bluestone, J. A. (1996) CD28/B7 system of T cell costimulation. Annu. Rev. Immunol. 14, 233–258.

    Article  CAS  PubMed  Google Scholar 

  47. Chambers, C. A. and Allison, J. P. (1997) Co-stimulation of T cell responses. Curr. Opin. Immunol. 9, 396–404.

    Article  CAS  PubMed  Google Scholar 

  48. Kim, J. J., Bagarazzi, M. L., Trivedi, N., Hu, Y., Kazahaya, K., Wilson, D. M., et al. (1997) Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes. Nature Biotechnol. 15, 641–646.

    Article  CAS  Google Scholar 

  49. Levitsky, H. I. (1997) Accessories for naked DNA vaccines. Nat. Biotechnol. 15, 619,620.

    Article  CAS  PubMed  Google Scholar 

  50. Sato, Y., Roman, M., Tighe, H., Lee, D., Corr, M., Nguyen, M.-D., et al. (1996) Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273, 352–354.

    Article  CAS  PubMed  Google Scholar 

  51. Klinman, D. M., Yi, A.-K., Beaucage, S. L., Conover, J., and Krieg, A. M. (1996) CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon γ. Proc. Natl. Acad. Sci. USA 93, 2879–2883.

    Article  CAS  PubMed  Google Scholar 

  52. Ballas, Z. K., Rasmussen, W. L., and Krieg, A. M. (1996) Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynmuclkeotides and bacterial DNA. J. Immunol. 157, 1840–1845.

    CAS  PubMed  Google Scholar 

  53. Klinman, D. M., Yamshchikov, G., and Ishigatsubo, Y. (1997) Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 158, 3635–3639.

    CAS  PubMed  Google Scholar 

  54. Stacey, K. J., Sweet, M. J., and Hume, D. A. (1996) Macrophages ingest and are activated by bacterial DNA. J. Immunol. 157, 2116–2122.

    CAS  PubMed  Google Scholar 

  55. Pisetzki, D. S. (1996) Immune activation by bacterial DNA: a new genetic code. Immunity 5, 303–310.

    Article  Google Scholar 

  56. Roman, M., Martin-Orozco, E., Goodman, J. S., Nguyen, M.-D., Sato, Y., Ronaghi, A., et al. (1997) Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat. Med. 3, 849–854.

    Article  CAS  PubMed  Google Scholar 

  57. Inaba, K., Inaba, M., Romani, N., Aya, H., Deguchi, M., Ikehara, S., et al. (1992) Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte-macrophage colony-stimulating factor. J. Exp. Med. 176, 1693–1702.

    Article  CAS  PubMed  Google Scholar 

  58. Caux, C., Dezutter-Damboyant C., Schmitt D., Bancherau, J. (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature (Lond.) 360, 258–262.

    Article  CAS  Google Scholar 

  59. Romani, N., Gruner, S., Brang, D., Kämpgen, E., Lenz, A., Trockenbacher, B., et al. (1994) Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180, 83–93.

    Article  CAS  PubMed  Google Scholar 

  60. Reid, C. D. (1997) The dendritic cell lineage in haemopoesis. Br. J. Haematol. 96, 217–223.

    Article  CAS  PubMed  Google Scholar 

  61. Austyn, J. M. (1998) Dendritic cells. Curr. Opin. Hematol. 5, 3–15.

    Article  CAS  PubMed  Google Scholar 

  62. Young, J. W. and Inaba, K. (1996) Dendritic cells as adjuvants for class I major histocompatibility complex-restricted antitumor-immunity. J. Exp. Med. 183, 7–11.

    Article  CAS  PubMed  Google Scholar 

  63. Schuler, G. and Steinman, R. M. (1997) Dendritic cells as adjuvants for immune-mediated resistance to tumors. J. Exp. Med. 186, 1183–1187.

    Article  CAS  PubMed  Google Scholar 

  64. Mayordomo, J. I., Zorina, T., Storkus, W. J., Celuzzi, C. M., Falo, L. D., Kast, W. M., et al. (1995) Bone marrow-derived dendritic cells pulsed with tumor peptides elicit protective and therapeutic anti-tumor immunity. Nat. Med. 1, 1297–1302.

    Article  CAS  PubMed  Google Scholar 

  65. Mayordomo, J. I., Loftus, D. J., Sakamoto, H., De Cesare, S. M., Appasamy, P. M., et al. (1996) Therapy of murine tumors with p53 wild-type and mutant sequence peptide-based vaccines. J. Exp. Med. 183, 1357–1365.

    Article  CAS  PubMed  Google Scholar 

  66. Porgador, A., Snyder, D., and Gilboa, E. (1996) Induction of antitumor immunity using bone marrow-generated dendritic cells. J. Immunol. 156, 2918–2926.

    CAS  PubMed  Google Scholar 

  67. Zitvogel, L., Mayordomo, J. I., Tjandrawan, T., DeLeo, A. B., Clarke, M. R., Lotze, M. T., et al. (1996) Therapy of murine tumors with tumor peptide pulsed dendritic cells: dependence on T cells, B7 costimulation, and Th1-associated cytokines. J. Exp. Med. 183, 87–97.

    Article  CAS  PubMed  Google Scholar 

  68. Celluzi, C. M., Mayordomo, J. I., Storkus, W. J., Lotze, M. T., and Falo, L. D. (1996) Peptide-pulsed dendritic cells induce antigen-specific, CTL-mediated protective tumor immunity. J. Exp. Med. 183, 283–387.

    Article  Google Scholar 

  69. Bakker, A. B. H., Marland, G., de Boer, A. J., Huijbens, J. F., Danen, E. H. J., Adema, G. J., et al. (1995) Generation of antimelanoma cytotoxic T lymphocytes from healthy donors after presentation of melanoma-associated antigen-derived epitopes by dendritic cells in vitro. Cancer Res. 55, 5330–5334.

    CAS  PubMed  Google Scholar 

  70. van Elsas, A., van der Burg, S. H., van der Minne, C. E., Borghi, M., Mourer, J. S., et al. (1996) Peptide-pulsed dendritic cells induce tumoricidal cytotoxic T lymphocytes from healthy donors against stably HLA-A*0201-binding peptides from the Melan-A/MART-1 self antigen. Eur. J. Immunol. 26, 1683–1689.

    Article  PubMed  Google Scholar 

  71. Tjandrawan, T., Mäurer, M. J., Castelli, C., Lotze, M. T., and Storkus, W. J. (1998) Autologous dendritiphages pulsed with synthetic or natural tumor peptides elicit tumor-specific CTL in vitro. J. Immunother. 21, 149–157.

    Article  CAS  PubMed  Google Scholar 

  72. Specht, J. M., Wang, G., Do, M. T., Lam, J. S., Royal, R. E., Reeves, M. E., et al. (1997) Dendritic cells retrovirally transduced with a model antigen gene are therapeutically effective against established pulmonary metastases. J. Exp. Med. 186, 1213–1221.

    Article  CAS  PubMed  Google Scholar 

  73. Nishioka, Y., Shurin, M., Robbins, P. D., Storkus, W. J., and Lotze, M. T. (1997) Effective tumro immunotherapy using bone marrow-derived dendritic cells genetically engineered to express interleukin 12. J. Immunother. 20, 419.

    Article  Google Scholar 

  74. Szabols, P., Gallardo, H. F., Ciocon, D. H., Sadelein, M., and Young, J. W. (1997) Retrovirally transduced human dendritic cells express a normal phenotype and potent T cell stimulatory capacity. Blood 90, 2160–2167.

    Google Scholar 

  75. Henderson, R. A., Nimgaonkar, M. T., Watkins, S. C., Robbins, P. D., Ball, E. D., and Finn, O. J. (1996) Human dendritic cells genetically engineered to express high levels of the human epithelial tumor antigen mucin (MUC-1). Cancer Res. 56, 3763–3770.

    CAS  PubMed  Google Scholar 

  76. Reeves, M. E., Royal, R. E., Lam, J. S., Rosenberg, S. A, and Hwu, P. (1996) Retroviral transduction of human dendritic cells with a tumor-associated antigen gene. Cancer Res. 56, 5672–5677.

    CAS  PubMed  Google Scholar 

  77. Aicher, A., Westermann, J., Cayeux, S., Willimsky, G., Daemen, K., Blankenstein, T., et al. (1997) Successful retroviral mediated transduction of a reporter gene in human dendritic cells: feasibility of therapy with gene-modified antigen presenting cells. Exp. Hematol. 25, 39–44.

    CAS  PubMed  Google Scholar 

  78. Smith, C. A., Woodruff, L. S., Kitchingman, G. R., Rooney, C. M. (1996) Adenovirus-pulsed dendritic cells stimulate human virus-specific T-cell responses in vitro. J. Virol. 70, 6733–6740.

    CAS  PubMed  Google Scholar 

  79. Arthur, J. F., Butterfield, L. H., Roth, M. D., Bui, L. A., Kiertscher, S. M., Lau, R., et al. (1997) A comparison of gene transfer methods in human dendritic cells. Cancer Gene Ther. 4, 17–25.

    CAS  PubMed  Google Scholar 

  80. Brossart, P., Goldrath, A. W., Butz, E. A., Martin, S., Bevan, M. J. (1997) Virus-mediated delivery of antigenic epitopes into dendritic cells as a means to induce CTL. J. Immunol. 158, 3270–3276.

    CAS  PubMed  Google Scholar 

  81. Ribas, A., Butterfield, L. H., McBride, W. H., Jilani, S. M., Bui, L. A., Vollmer, C. M., et al. (1997) Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant adenovirus-transduced murine dendritic cells. Cancer Res. 57, 2865–2869.

    CAS  PubMed  Google Scholar 

  82. Wan, Y., Bramson, J., Carter, R., Graham, F., and Gauldie, J. (1997) Dendritic cells transduced with an adenoviral vector encoding a model tumor-associated antigen for tumor vaccination. Hum. Gene Ther. 8, 1355–1363.

    Article  CAS  PubMed  Google Scholar 

  83. Song, W., Kong, H.-L., Carpenter, H., Torii, H., Granstein, R., Rafii, S., et al. (1997) Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity. J. Exp. Med. 186, 1247–1256.

    Article  CAS  PubMed  Google Scholar 

  84. Kim, C. J., Prevette, T., Cormier, J., Overwijk, W., Roden, M., Restifo, N. P., et al. (1997) Dendritic cells infected with poxviruses encoding MART-1/Melan A sensitize T lymphocytes in vitro. J. Immunother. 20, 276–286.

    Article  CAS  PubMed  Google Scholar 

  85. Alijagic, S., Moller, P., Artuc, M., Jurgovsky, K., Czarnetzki, B. M., and Schadendorf, D. (1995) Dendritic cells generated from peripheral blood trans-fected with human tyrosinase induce specific T cell activation. Eur. J. Immunol. 25, 3100–3107.

    Article  CAS  PubMed  Google Scholar 

  86. Tüting, T., Wilson, C. C., Martin, D., Kasamon, Y., Rowles, J., Ma, D. I., et al. (1998) Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-α. J. Immunol. 160, 1139–1147.

    PubMed  Google Scholar 

  87. Tüting, T., DeLeo, A., Lotze, M. T., Storkus, W. J. (1997) Bone marrow-derived dendritic cells genetically-modified to express tumor-associated antigens induce antitumor immunity in vivo. Eur. J. Immunol. 27, 2702–2707.

    Article  PubMed  Google Scholar 

  88. Manickan, E., Kanangat, S., Rouse, R. J. D., Yu, Z., Rouse, B. T. (1997) Enhancement of immune response to naked DNA vaccine by immunization with trans-fected dendritic cells. J. Leukocyte Biol. 61, 125–132.

    CAS  PubMed  Google Scholar 

  89. Martinon, F., Krishnan, S., Lenzen, G., Magne, R., Gomard, E., Guillet, J.-G., et al. (1993) Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA. Eur. J. Immunol. 23, 1719–1722.

    Article  CAS  PubMed  Google Scholar 

  90. Conry, R. M., LoBuglio, A. F., Wright, M., Sumerel, L., Pike, M. J., Johanning, F., et al. (1995) Characterization of a messenger RNA polynucleotide vaccine vector. Cancer Res. 55, 1397–1400.

    CAS  PubMed  Google Scholar 

  91. Qiu, P., Ziegelhoffer, P., Sun, J., and Yang, N. S. (1996) Gene gun delivery of mRNA in situ results in efficient transgene expression and genetic immunization. Gene Ther. 3, 262–268.

    CAS  PubMed  Google Scholar 

  92. Boczkowski, D., Nair, S. K., Snyder, D., and Gilboa, E. (1996) Dendritic Cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J. Exp. Med. 184, 465–472.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA

    Thomas Tüting & Walter J. Storkus

  2. Nuffield Department of Surgery, University of Oxford, Oxford, UK

    Jonathan Austyn

  3. Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, PA

    Louis D. Falo Jr.

Authors
  1. Thomas Tüting
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan Austyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Walter J. Storkus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Louis D. Falo Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Mycobacterial Research Laboratory, London, UK

    Douglas B. Lowrie MD

  2. Maxygen Inc., Redwood City, CA

    Robert G. Whalen MD

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Tüting, T., Austyn, J., Storkus, W.J., Falo, L.D. (2000). The Immunology of DNA Vaccines. In: Lowrie, D.B., Whalen, R.G. (eds) DNA Vaccines. Methods in Molecular Medicine™, vol 29. Humana Press. https://doi.org/10.1385/1-59259-688-6:37

Download citation

  • DOI: https://doi.org/10.1385/1-59259-688-6:37

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-580-5

  • Online ISBN: 978-1-59259-688-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation